Cerebrospinal fluid (CSF), or liquor cerebrospinalis, is found in the subarachnoid space as well as in the ventricles surrounding and penetrating the central nervous system (CNS). CSF bathes the brain and spinal cord and provides hydrative, nutritive, metabolic waste removal, and hydrostatic impact buffer to neurons and glia. CSF is produced from arterial blood by the choroid plexuses of the lateral and fourth ventricles by a combined process of diffusion, pinocytosis and active transfer. The fluid also contains constituents produced by neurons and glia. After diffusion through the ventricular system into the subarachnoid space, most of the CSF is reabsorbed by the arachnoid granulations to reenter the blood stream via the dural venous plexus. Approximately 500 ml of liquor is generated every day; with a total volume of 140-150 ml for an adult, the whole CSF is renewed every 6-8 hours. The CSF is bounded by the dura throughout the CNS. More fluid is produced in the rostral CNS and more ultimately drains in the caudal spinal cord to produce a net rostral to caudal fluid flow. CSF is an isotonic mixture mostly of salts, glucose, protein and water. CSF from the lumbar region contains 15 to 45 mg/dl protein (0.3-1% of serum protein concentration) and 50-80 mg/dl glucose (60% of blood glucose). Protein concentration in cisternal and ventricular CSF is lower.
The protein landscape of the CSF can be divided into two groups: Blood derived proteins, which make up the main fraction in the CSF of healthy individuals, and brain derived proteins. Approximately 20% of the proteins in the CSF originate from the brain parenchyma, but only a subset of those are actually brain specific.
Despite the fact that the majority of liquor proteins are also found in the serum, there are multiple sources for proteins unique to the CSF:
Proteins that are released from neurons and glial cells, e.g. tau protein, S-100, and neuron-specific enolase (NSE).
Proteins released from leptomeniges, e.g. β-trace protein and cystatin C.
Proteins differentially modified by glycosylation or phosphorylation during synthesis in the choroid plexus, e.g. transthyretin (TTR), angiotensin II, and Insulin-like growth factor II.
There is substantial overlap in the protein profile between CSF and plasma, a considerable number of proteins are unique to the CSF or are uniquely modified by phosphorylation or glycosylation in the CNS.
Lateral Flow Tests, or also known as Lateral Flow Immunochromatographic Assays or Strip Tests, are designed to rapidly detect the presence or absence of a given analyte in a heterogenous matrix. A variety of Lateral Flow Tests are currently on the market for home testing, point of care testing, or laboratory use, for instance pregnancy tests (e.g., FirstResponse®, ClearBlue®), HIV tests (e.g., OraQuick ADVANCE®, Clearview® Complete), or Chlamydia tests (e.g., Clearview® Chlamydia, inSTIcheck™ Chlamydia).
What is needed is a test suitable for detection of CSF that is comparable to HIV tests like OraQuick ADVANCE® or Clearview® Complete: It is a point of care test; the test is only qualitative; the operator needs minimal training to use the test; the test has an internal control on the strip to verify accurate sampling.